Uterus Transplantation: Where are We Today?

Uterus transplantation (UTx) has in recent years been demonstrated to provide a route to having their own genetic child for women with absolute uterine factor infertility (AUFI), whose only other option to attain biological motherhood would be surrogacy. AUFI may be acquired as a result of hysterectomy for benign or malignant disease or due to iatrogenic loss of uterine function. However, AUFI can also occur congenitally as in Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), also known as utero-vaginal aplasia or Müllerian agenesis. This rare female genital malformation affects about one in 4000 –5000 live female births. Genetically, women with MRKHS are females with a normal 46, XX karyotype, but phenotypically they lack a vagina (vaginal aplasia) and uterus (uterine aplasia). However, as they have functional ovaries, girls with MRKHS develop normal secondary sexual characteristics, including breast growth and body hair. The primary diagnosis of MRKHS is generally made relatively late, often only when menstruation fails to set in at the onset of puberty or, less frequently, when they are unable to have vaginal sexual intercourse. Hence, the first treatment goal in MRKHS is to enable the patient to have vaginal intercourse “like any other woman”. To this end, our team developed and optimized a minimally invasive technique that creates a neovagina with a functional epithelial lining, enabling normal sexual intercourse and orgasm ability. The procedure is fast, effective, and minimally traumatic, has a very low complication rate, and produces excellent longterm functional results, including the correct anatomical axis. The ultimate treatment goal is to give MRKHS patients the opportunity to experience pregnancy and childbirth. With the advent of UTx in recent years, transplantation provides the only alternative to surrogacy in many countries, such as Germany, where surrogacy is prohibited by law. In such countries, UTx is the only future option these women have to conceive their own biological children. Human living-donor (LD) UTx was established in Sweden after meticulous, systematic animal-based research. The first livebirth after human LD-UTx was performed in Gothenburg (Sweden) in 2014. The development of the UTx technique in Sweden was preceded by, and progressed in parallel with, basic experimental and clinical research by our multidisciplinary teams with regard to neovaginoplasty and patient evaluation for UTx eligibility. The first UTx in Germany was performed at Tübingen University Hospital in collaboration with the Gothenburg team in 2016, marking the initiation of the hitherto only clinical UTx program in Germany. Establishment of our UTx program incorporated advice from several institutions, including the Ethical Committee of the University of Tübingen, the Standing Organ Transplantation Committee of the German Medical Association, the Baden-Württemberg State Board of Physicians, the Living Donor Committee of the District Chamber of Physicians, and the Multidisciplinary Transplantation Board of Tübingen University Hospital. Our approach is to provide gynecological, surgical, fertility, UTx, and obstetric services for women with AUFI to offer them a route to biological motherhood. As of May 2022, 4 LD-UTx procedures had been performed in Germany, all of them at our hospital. Each patient has given birth to a healthy child, and the first child is now 3 years old. Tübingen University Hospital so far is the only official UTx center approved by the Baden-Württemberg Ministry of Social Affairs and health insurance providers. In many respects, UTx is still clinically in the experimental phase, warranting further research. Hence, data need to be collected in an international registry such as the one recently initiated by the International Society of Uterus Transplantation (ISUTx).